Réaction #2254167

ord-9286f1e0b8d6469f889b307efcc0fa1f

Équation de réaction

CC#N
acetonitrile
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
glucose
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
GLU
O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
GLU
→
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC.O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
TAC GLU

Réactifs

CC#N
acetonitrile
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
glucose
—
solids
C=CC[C@@H]1/C=C(\C)C[C@H](C)C[C@H](OC)[C@H]2O[C@@](O)(C(=O)C(=O)N3CCCC[C@H]3C(=O)O[C@H](/C(C)=C/[C@@H]3CC[C@@H](O)[C@H](OC)C3)[C@H](C)[C@@H](O)CC1=O)[C@H](C)C[C@@H]2OC
TAC
O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
GLU
O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
GLU

Réactifs

Aucun

Solvants

O
water

Conditions de réaction

Température
-50°CELSIUS
Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    AutreThe composition was prepared
  2. 2
    Températureis cooled
  3. 3
    AutreThe frozen compositions were then collected
  4. 4
    Autrethe solvent was removed by lyophilization
  5. 5
    Autrewere stored at room temperature under vacuum
  6. 6
    AutreThe result of XRD characterization (
  7. 7
    AutreThe result of SEM (

Mode opératoire

A formulation of tacrolimus (TAC) was produced using TAC and glucose (GLU) in ratio 1:1. The TAC:GLU 1:1 formulation was prepared using the ultra-rapid freezing (URF) process. The composition was prepared by dissolving TAC and GLU at a 1:1 ratio and 0.75% solids in a 60/40 mixture of acetonitrile and water. The solution of drug and excipient was applied to the surface of a solid substrate, which is cooled using a cryogenic substrate maintained at −50° C. The frozen compositions were then collected and the solvent was removed by lyophilization using a VirTis Advantage Lyophilizer (VirTis Company, Inc. Gardiner, N.Y.). The dried powders were stored at room temperature under vacuum. The result of XRD characterization (following the procedure in example 2) is that the formulation is amorphous. The result of SEM (following the procedure in example 4) is that the morphology is nanostructured aggregates with small primary particles consisting of TAC and GLU with primary particle sizes of about 100-300 nm.

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US09044391B2uspto-grants-2015_06